5'tiRNA-Glu-TTC targets TRPV3 and activates the PI3K/AKT signaling pathway to modulate skin photoaging.

tRNA-derived small RNAs (tsRNAs), a class of non-coding RNAs (ncRNAs), have garnered increasing research interest for their potential roles in various biological processes. Among these, 5'tiRNA-Glu-TTC has been implicated in aging, but its role in skin photoaging remains elusive. This study aimed to elucidate the impact of 5'tiRNA-Glu-TTC on skin photoaging. RT-qPCR analysis revealed that 5'tiRNA-Glu-TTC expression increased in human dermal fibroblasts (HDFs), human skin tissues, and mouse skin tissues following UVB irradiation. In HDFs, transfection of a 5'tiRNA-Glu-TTC mimic induced photoaging phenotypes, while its inhibitor alleviated UVB-induced photoaging. This study found that 5'tiRNA-Glu-TTC participates in photoaging through binding to TRPV3. Overexpression of TRPV3 rescued the photoaging effects induced by the 5'tiRNA-Glu-TTC mimic. Furthermore, 5'tiRNA-Glu-TTC influences photoaging also by activating the PI3K/AKT signaling pathway, an effect that was reversed by TRPV3 overexpression. In vivo studies in nude mice showed that intradermal injection of 5'tiRNA-Glu-TTC adeno-associated virus alleviated UVB-induced skin aging phenotypes, including epidermal thickening, dermal collagen reduction, and increased transepidermal water loss (TEWL). Collectively, our findings demonstrate that 5'tiRNA-Glu-TTC mediates photoaging by targeting TRPV3 and activating the PI3K/AKT pathway.